Mechanisms and Some Causes of Jaundice in Adults

Unconjugated hyperbilirubinemia

Increased bilirubin production

Common: Hemolysis

Less common: Resorption of large hematomas, ineffective erythropoiesis

Few or no clinical manifestations of hepatobiliary disease; sometimes anemia, ecchymoses

Serum bilirubin level usually < 3.5 mg/dL (< 59 micromol/L), no bilirubin in urine, normal aminotransferase levels

Decreased hepatic bilirubin uptake

Common: Heart failure

Less common: Drugs, fasting, portosystemic shunts

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Decreased hepatic conjugation

Common: Gilbert syndrome

Crigler-Najjar syndrome, hyperthyroidism

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Conjugated hyperbilirubinemia†

Hepatocellular dysfunction

Common: Drugs, toxins, viral hepatitis

Less common: Alcohol-related liver disease, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, steatohepatitis, Wilson disease

Aminotransferase levels usually > 500 U/L (8.35 microkat/L)

Intrahepatic cholestasis

Common: Alcohol-related liver disease, drugs, toxins, viral hepatitis

Less common: Infiltrative disorders (eg, amyloidosis, lymphoma, sarcoidosis, tuberculosis), pregnancy, primary biliary cholangitis, steatohepatitis

Gradual onset of jaundice, sometimes pruritus

If severe, clay-colored stools, steatorrhea

If long-standing, weight loss

Alkaline phosphatase and GGT usually > 3 times normal

Aminotransferase levels < 200 U/L (3.34 microkat/L)

Extrahepatic cholestasis

Common: Common bile duct stone, pancreatic cancer

Less common: Acute cholangitis, pancreatic pseudocyst, primary sclerosing cholangitis, common duct strictures caused by previous surgery, other tumors

Depending on cause, manifestations possibly similar to those of intrahepatic cholestasis or a more acute disorder (eg, abdominal pain or vomiting due to a common bile duct stone or acute pancreatitis)

Alkaline phosphatase and GGT usually > 3 times normal

Aminotransferase levels < 200 U/L (3.34 microkat/L)

Other, less common mechanisms

Hereditary disorders (mainly Dubin-Johnson syndrome and Rotor syndrome)

Normal liver enzymes